Wednesday, December 28, 2011

An end to Ediacaran embryology?

The things people can do these days. Therese Huldtgren and colleagues reported in last week's Science that they identified nucleus-like structures in 570 million year old fossilized cells from China. These date to the Ediacaran period, before the "Cambrian explosion" of animal life forms. Superficially, these fossilized balls of cells rather resemble the early stages of animal embryos (see A in the figure below), in which cells are dividing and increasing in number but the overall embryo size stays the same. To get the "inside story" (...sorry), Huldtgren and team used very fancy "synchrotron x-ray computed tomography" to look at the insides of these fossilized cells. The resulting images have micrometer resolution - that's one thousandth* of a millimeter. The things people can do these days.

Fig. 2 from Huldtgren et al. 2011
And lo! each of these fossilized cells contains a small, globular structure that looks like a nucleus (left; if you cross your eyes you can merge the 2 halves of fig. C to make it look even more 3D).

Could these really be the earliest animal embryos? Probably not - some of these balls-of-cells had what resemble budding spores, unlike animals but similar to "nonmetazoan [non-animal] holozoans." In other words, something neat and old, but not one of our earliest ancestors.

I'm really impressed with the biological applications of computed tomography (CT). Recall that a while ago, I posted about the potential to use synchrotron tomography to examine the small-scale, internal structure of bone (e.g. Cooper et al. 2011). Such non-destructive, high-resolution imaging techniques could be used to compare near-cellular-level growth in living and fossil animals. This is really significant because it adds a completely new kind of information we can get from fossils, which before now could only be studied well at the gross, macroscopic level (though scanning electron microscopy of teeth has been very informative about diet; see for example Ungar and Sponheimer 2011). Indeed, one of the most common applications of CT imaging in anthropology is making 3D computer models of body parts for morphometric (shape) analysis.

But high-resolution, synchrotron CT imaging opens up a whole new world of paleontology, new questions that can be asked. For example, many researchers have examined the microscopic appearance of bone surfaces to determine whether bone was being added or removed during growth, and comparing different species (Bromage 1989, O'Higgins et al. 2001, McCollum 2008, Martinez-Mata et al. 2010). These have been very informative studies, but it is not totally clear how growth at the cellular level relates to growth at visible level. Moreover, fossil surfaces are often abraded, obfuscating surface details. So, I can envision using synchrotron microscopy similar to Cooper et al. (2011) and Huldtgren et al. (2011), to examine bone growth in fossil hominids, at and beneath the surface. This can help us understand how facial growth was modified over the course of human evolution, from the snouty visage of Australopithecus afarensis to the tiny, starry-eyed faces we have today. People could also examine how activities like chewing, running or even talking affect (and effect) bone growth. There is much work to be done.

ResearchBlogging.orgNeat as these projects would be, it's pretty humbling to consider that we have the technology to analyze microscopic fossils hundreds of millions of years old, and shed light on the developmental processes in our earliest ancestors.

Read those things I'd mentioned
BROMAGE, T. (1989). Ontogeny of the early hominid face Journal of Human Evolution, 18 (8), 751-773 DOI: 10.1016/0047-2484(89)90088-2

Cooper, D., Erickson, B., Peele, A., Hannah, K., Thomas, C., & Clement, J. (2011). Visualization of 3D osteon morphology by synchrotron radiation micro-CT Journal of Anatomy, 219 (4), 481-489 DOI: 10.1111/j.1469-7580.2011.01398.x

Huldtgren, T., Cunningham, J., Yin, C., Stampanoni, M., Marone, F., Donoghue, P., & Bengtson, S. (2011). Fossilized Nuclei and Germination Structures Identify Ediacaran "Animal Embryos" as Encysting Protists Science, 334 (6063), 1696-1699 DOI: 10.1126/science.1209537

Martinez-Maza, C., Rosas, A., & Nieto-Diaz, M. (2010). Brief communication: Identification of bone formation and resorption surfaces by reflected light microscopy American Journal of Physical Anthropology, 143 (2), 313-320 DOI: 10.1002/ajpa.21352

McCollum, M. (2008). Nasomaxillary remodeling and facial form in robust Australopithecus: a reassessment Journal of Human Evolution, 54 (1), 2-14 DOI: 10.1016/j.jhevol.2007.05.013

O'Higgins, P., Chadfield, P., & Jones, N. (2001). Facial growth and the ontogeny of morphological variation within and between the primates Cebus apella and Cercocebus torquatus Journal of Zoology, 254 (3), 337-357 DOI: 10.1017/S095283690100084X

Ungar, P., & Sponheimer, M. (2011). The Diets of Early Hominins Science, 334 (6053), 190-193 DOI: 10.1126/science.1207701

Friday, December 23, 2011

Ancient DNA & admixture: One of Science's breakthrough in 2011

The high-profile journal Science has compiled a list of the top breakthroughs of 2011, some of the most major discoveries and and advances across scientific fields. The top breakthrough was research finding that antiretroviral drugs can act not only to treat patients infected with HIV, but also these antiretrovirals significantly reduce the likelihood of transmission of the disease. This is a pretty effing big deal, as HIVand AIDS are tragically rampant in many parts of the world.

One of the runners-up to this breakthrough: "Archaic Humans' DNA lives on." The brief exposé highlights the studies from this year that corroborated the 2010 evidence for Neandertal and "Denisovan" DNA in living people. The exposé concludes with a short and rather out-of-the-blue paragraph about the Australopithecus sediba fossils from Malapa. How about that - anthropological research as a major scientific breakthrough; FL governor Rick Scott certainly didn't see that one coming.
See for yourself:
Anonymous (2011). The Runners-Up Science, 334 (6063), 1629-1635 DOI: 10.1126/science.334.6063.1629

Thursday, December 22, 2011

My X-mas gift - a clear passing lane

I just drove from MI to MO to visit my awesome family for the holiday. I'm glad to have the chance to spend this special time with the people I love.

But the 12-hour drive today reminded me: one of the greatest gifts you can give me and the rest of America is courteous driving on the highway. Specifically, if you are not passing anyone (on your right), then YOU NEED TO GET THE F OUT OF THE LEFT LANE (sound familiar?). If we hang out in the right lane and enter the left only to pass another car when necessary, well the world will be a better place.
Map of the Dwight D. Eisenhower System of Interstate and Defense Highways. That's what it's actually called. "Defense" refers to the most insidious of our intrinsic insecurities - bad drivers. Image:
Don't get me wrong. I am very impressed that you have the brightest f*ing headlights on the market, so that once I finally get to pass you - dangerously on the right - seeing you in my rearview mirror is like staring at the sun. But all the headlights in the world don't make it alright for you to just camp out in the left lane, not passing anyone, clotheslining 2 lanes of traffic, and probably eventually leading to the shutdown of the highway system that Eisenhower and the dying American auto industry created for your enjoyment.

Also, just so we're clear: If you 1) camp in the fast lane, and/or 2) have gratuitously bright headlights, you are the worst person in the world.

Friday, December 16, 2011

Small-stranded insanity inside your cells

The Nature News Blog posted a fascinating video showing how RNA interference (RNAi) works within a cell. RNAi refers to the regulation of gene expression by short-length RNAs. So far as I understand it, there are a number of types of small stretches of RNA (e.g. siRNApiRNA) that do not code for proteins but rather target other RNAs, and then latch onto them via proteins to ensure the other RNA's demise.  RNAi is implicated in expression of lots of genes, for instance HOTAIR is a long intergenic noncoding RNA that is itself located in the HOXC cluster but later acts to repress HOXD expression (Woo and Kingston 2007).

The video (there's also a slideshow) provides a stunning and digestible visual of what exactly is going on during this complex process. It's online and it's completely free (see links above), and so could be a valuable resource for teaching about this aspect of gene regulation.

Oh, the humanity. An Argonaute protein is guided by a small interfering RNA to where it will start rending a messenger RNA. From this great slideshow by Nature Reviews Genetics and Arkitek.
Some RNAi reviews
Czech, B., & Hannon, G. (2010). Small RNA sorting: matchmaking for Argonautes Nature Reviews Genetics, 12 (1), 19-31 DOI: 10.1038/nrg2916

Moss, E. (2001). RNA interference: It's a small RNA world Current Biology, 11 (19) DOI: 10.1016/S0960-9822(01)00467-5

Woo, C., & Kingston, R. (2007). HOTAIR Lifts Noncoding RNAs to New Levels Cell, 129 (7), 1257-1259 DOI: 10.1016/j.cell.2007.06.014

Anton Wutz (2011). RNA-Mediated Silencing Mechanisms in Mammalian Cells Progress in Molecular Biology and Translational Science, 101, 351-376 DOI: 10.1016/B978-0-12-387685-0.00011-1

UPDATE: The Journal of Experimental Zoology B has an entire issue dedicated to "RNA in Developmental Evolution."

Tuesday, December 13, 2011

Humans and snakes, beyond the Garden

There's a paper in press in PNAS describing human-snake relations among Agta hunter-gatherers in the Philippines. The paper is pretty neat, as it describes a pretty complex relationship between, in this case, reticulated pythons and humans (and generally between other snakes and primates). Humans have been attacked (and presumably eaten) by large pythons. Conversely, Agta have killed and eaten pythons. There is also a good deal of overlap in prey species eaten by humans and pythons. So at once, the relationship between humans (at least the Agta) and pythons could be described as predator-prey, prey-predator and competitors; given this dynamic, maybe Genesis readers should be more surprised that Eve and the serpent didn't try to eat one another.

The paper also has some great pictures of a huge python that was killed and flayed by an Agta group in the early 1970s (check it out free with more coverage at ScienceMag). At right is another sweet pic from the paper, an X-ray of a snake that has swallowed whole TWO juvenile monkeys!

On the far right you can clearly see the head and spine of one, and on the left half by the 'bend' in the snake you can see the head, spine and upper limb of the other, its legs visible in the bottom left corner. Nuts!

The authors write that because of the swallow-whole style that pythons ingest their prey, it may be impossible to determine whether fossil hominids fell prey to such a swallowing serpent. But I think this is itself a potentially testable hypothesis. If the snake X-rayed above was alive, researchers could have waited for the snake to expel its stomach contents, to see if death-by-python leaves any special signatures on the skeleton. Stomach acids the used by the snake to digest prey may leave a special mark on bone; because constricting snakes usually squeeze the ** out of their prey to subdue them, this could result in a characteristic pattern of bone breakage [Briana Pobiner and colleagues (2007) did a similar study based on the skeletal aftermaths of chimpanzee hunts]. So f we know what a snake's primate meal looks like when vacated, we could potentially see if there are any such serpentine signatures in the fossil record. Assuming that swallowed-by-snake could be detected, even if no fossil hominids (or apes and monkeys, for that matter) bear such signatures, that doesn't mean it didn't happen, but simply that we can't say for sure whether it did.

Headland, T., & Greene, H. (2011). PNAS Plus: Hunter-gatherers and other primates as prey, predators, and competitors of snakes Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1115116108

Pobiner, B., DeSilva, J., Sanders, W., & Mitani, J. (2007). Taphonomic analysis of skeletal remains from chimpanzee hunts at Ngogo, Kibale National Park, Uganda Journal of Human Evolution, 52 (6), 614-636 DOI: 10.1016/j.jhevol.2006.11.007

Saturday, December 10, 2011

The next big thing? Automated methods in biology, or "Hooked on phenomics"

"This is very beautiful. It is neat, it is modern technology, and it is fast. I am just wondering very seriously about the biological validity of what we are doing with this machine." - Melvin Moss, 1967*
"This machine" to which Moss referred nearly 50 years ago was not a contraption to clone a Neandertal or a Godzilla-like MechaGodzilla, but a computer. Along these lines, a paper came out recently describing a new, automated method for analyzing (biological) shapes, and while I think the method is pretty sweet, I think future researchers employing it should keep Moss's monition in mind.

Doug Boyer and colleagues (2011) present "Algorithms to automatically quantify the geometric similarity of anatomical surfaces." It seems the main goals of the study were to make shape analysis [1] faster and [2] easier for people who don't otherwise study anatomy (such as geneticists), making it possible [3] to amass large phenotypic datasets comparable to the troves of genetic data accumulated in recent years. Using some intense math that's way over my head, the computer algorithm takes surface data (acquired through CT or laser scans) of a pair of specimens and automatically fits these forms with a "correspondence map" linking geometrically (and not necessarily biologically) homologous features between the two. It then uses the map to fit landmarks (a la geometric morphometrics) which are used to calculate the shape difference metric between individuals in the pairings.

See at the right just how pretty it is! The authors posit that this technique could be used with genetic knock-out studies to assess how certain genes affect the development of bones and teeth, or to model the development of organs. That certainly would be useful in biomedical and evo-devo research.

But while I appreciate the automated-ness of the procedure, I don't think we can simply write off the role of the biologist in determining what features are homologous, in favor of a computer. The paper itself illustrates this nicely. The authors state that there is debate about the origins of a cusp on the molar tooth of the sportive lemur (Lepilemur) - is it the same as the entoconid of the living mouse lemur, or the enlarged metaconid of the extinct "koala lemur"? Their automated algorithm can map the sportive lemur's mystery cusp to match either alternative scenario. It is the external paleontological and phylogenetic evidence, not the intrinsic shape information, that renders the alternative scenario more plausible.
So let me reiterate that I think this paper presents an important step for the study of the biology of form, or the form of biology. Automating the analysis of form will certainly expedite studies of large datasets (not to mention freeing up the time of hordes of research assistants). But I hope that researchers employing this procedure will have a little Mossian Angel (poor play on "guardian angel," sorry) on their shoulders, reminding them that the algorithm won't necessarily show them homology better than their own experience. And I hope all biologists have this Mossian Angel there, reminding them that even though this method is "neat ... modern technology, and ... fast," it may not be the most appropriate method for their research question.

Boyer, D., Lipman, Y., St. Clair, E., Puente, J., Patel, B., Funkhouser, T., Jernvall, J., & Daubechies, I. (2011). Algorithms to automatically quantify the geometric similarity of anatomical surfaces Proceedings of the National Academy of Sciences, 108 (45), 18221-18226 DOI: 10.1073/pnas.1112822108

*This quote comes from a discussion at the end of a symposium: Cranio-Facial Growth in Man (1967). RE Moyers and WM Krogman, editors. New York: Pergamon Press.